This invention relates to formulations and methods for enhancing the efficacy of exogenous chemicals used in treating plants. An exogenous chemical, as defined herein, is any chemical substance, whether naturally or synthetically derived, which (a) has biological activity or is capable of releasing in a plant an ion, moiety or derivative which has biological activity, and (b) is applied to a plant with the intent or result that the chemical substance or its biologically active ion, moiety or derivative enter living cells or tissues of the plant and elicit a stimulatory, inhibitory, regulatory, therapeutic, toxic or lethal response in the plant itself or in a pathogen, parasite or feeding organism present in or on the plant. Examples of exogenous chemical substances include, but are not limited to, chemical pesticides (such as herbicides, algicides, fungicides, bactericides, viricides, insecticides, aphicides, miticides, nematicides, molluscicides, and the like), plant growth regulators, fertilizers and nutrients, gametocides, defoliants, desiccants, mixtures thereof, and the like.
Exogenous chemicals, including foliar-applied herbicides, have at times been formulated with surfactants, so that when water is added, the resulting sprayable composition is more easily and effectively retained on the foliage (e.g., the leaves or other photosynthesizing organs) of plants. Surfactants can also bring other benefits, including improved contact of spray droplets with a waxy leaf surface and, in some cases, improved penetration of the accompanying exogenous chemical into the interior of leaves. Through these and perhaps other effects, surfactants have long been known to increase the biological effectiveness of herbicide compositions, or other compositions of exogenous chemicals, when added to or included in such compositions. Thus, for example, the herbicide glyphosate (N-phosphonomethylglycine) has been formulated with surfactants such as polyoxyalkylene-type surfactants including, among other surfactants, polyoxyalkylene alkylamines. Commercial formulations of glyphosate herbicide marketed under the trademark ROUNDUP(copyright) have been formulated with a surfactant composition based on such a polyoxyalkylene alkylamine, in particular a polyethoxylated tallowamine, this surfactant composition being identified as MON 0818. Surfactants have generally been combined with glyphosate or other exogenous chemicals either in a commercial concentrate (herein referred to as a xe2x80x9ccoformulationxe2x80x9d), or in a diluted mixture that is prepared from separate compositions, one comprising an exogenous chemical (e.g. glyphosate) and another comprising surfactant, prior to use in the field (i.e., a tank mix).
Various combinations of exogenous chemicals and surfactants or other adjuvants have been tested in the past. In some instances, the addition of a particular surfactant has not produced uniformly positive or negative changes in the effect of the exogenous chemical on the plant (e.g., a surfactant that may enhance the activity of a particular herbicide on certain weeds may interfere with, or antagonize, the herbicidal efficacy on another weed species).
Some surfactants tend to degrade fairly rapidly in aqueous solutions. As a result, surfactants that exhibit this property can only be used effectively in tank mixes (i.e., mixed with the other ingredients in solution or dispersion in the tank soon before spraying is to occur), rather than being coformulated in an aqueous composition with the other ingredients in the first instance. This lack of stability, or inadequate shelf-life, has hindered the use of certain surfactants in some exogenous chemical formulations.
Other surfactants, though chemically stable, are physically incompatible with certain exogenous chemicals, particularly in concentrate coformulations. For example, most classes of nonionic surfactant, including polyoxyethylene alkylether surfactants, do not tolerate solutions of high ionic strength, as for example in a concentrated aqueous solution of a salt of glyphosate. Physical incompatibility can also lead to inadequate shelf-life. Other problems that can arise from such incompatibility include the formation of aggregates large enough to interfere with commercial handling and application, for example by blocking spray nozzles.
Another problem that has been observed in the past is the effect of environmental conditions on uptake of an exogenous chemical composition into foliage of a plant. For example, conditions such as temperature, relative humidity, presence or absence of sunlight, and health of the plant to be treated, can affect the uptake of a herbicide into the plant. As a result, spraying exactly the same herbicidal composition in two different situations can result in different herbicidal control of the sprayed plants.
One consequence of the above-described variability is that often a higher rate of herbicide per unit area is applied than might actually be required in that situation, in order to be certain that adequate control of undesired plants will be achieved. For similar reasons, other foliar-applied exogenous chemicals are also typically applied at significantly higher rates than needed to give the desired biological effect in the particular situation where they are used, to allow for the natural variability that exists in efficiency of foliar uptake. A need therefore exists for compositions of exogenous chemicals that, through more efficient uptake into plant foliage, allow reduced use rates.
Many exogenous chemicals are commercially packaged as a liquid concentrate that contains a significant amount of water. The packaged concentrate is shipped to distributors or retailers. Ultimately the packaged concentrate ends up in the hands of an end user, who further dilutes the concentrate by adding water in accordance with label instructions on the package. The dilute composition thus prepared is then sprayed on plants.
A significant portion of the cost of such packaged concentrates is the cost of transporting the concentrate from the manufacturing site to the location where the end user purchases it. Any liquid concentrate formulation that contained relatively less water and thus more exogenous chemical would reduce the cost per unit amount of exogenous chemical. However, one important limit on the ability of the manufacturer to increase the loading of the exogenous chemical in the concentrate is the stability of that formulation. With some combinations of ingredients, a limit will be reached at which any further reduction of water content in the concentrate will cause it to become unstable (e.g., to separate into discrete layers), which may make it commercially unacceptable.
Accordingly, a need exists for improved formulations of exogenous chemicals, particularly herbicides, that are stable, effective, less sensitive to environmental conditions, and permit the use of reduced amounts of exogenous chemical to achieve the desired biological effect in or on plants. A need also exists for stable liquid concentrate formulations of exogenous chemicals that contain less water and more exogenous chemical than prior art concentrates.
The present invention relates to novel methods and compositions wherein exogenous chemicals are applied to plants to generate a desired biological response.
One embodiment of the present invention is a method of applying an exogenous chemical to a plant, comprising the steps of (a) contacting foliage of the plant with a biologically effective amount of the exogenous chemical, and (b) contacting the same foliage with an aqueous composition that comprises a first excipient substance that is amphiphilic. The weight/weight ratio of said first excipient substance to the exogenous chemical is between about 1:3 and about 1:100. Further, the aqueous composition forms anisotropic aggregates in or on a wax layer as explained below. xe2x80x9cContactingxe2x80x9d in this context means placing the substance or composition on the foliage. xe2x80x9cAmphiphilicxe2x80x9d means having at least one polar, water-soluble head group which is hydrophilic and at least one water-insoluble organic tail which is hydrophobic, contained within the same molecule.
In this method, step (b) can occur simultaneously with or within about 96 hours before or after step (a). In embodiments of the method in which the two steps occur simultaneously, either the exogenous chemical and the aqueous composition can be applied to the plant separately, for example by two spray nozzles directed at the same foliage, or the exogenous chemical can be contained within the aqueous composition, for example in a tank mix or coformulation.
Formation of anisotropic aggregates in or on a wax layer is determined by a test described in detail subsequently herein. In general, the test, as it applies to a composition comprising an exogenous chemical, comprises the steps of (1) providing a glass microscope slide coated with a thin, uniform layer of wax, such that the wax layer on the slide exhibits a dark field when illuminated by transmitted polarized light and examined through a microscope, (2) preparing a sample of an aqueous solution or dispersion of the composition to be tested, diluted or concentrated if necessary such that the concentration of exogenous chemical is about 15% to about 20% by weight of the composition, (3) positioning the wax-coated slide on the stage of a microscope that transmits polarized light through the slide, (4) placing a drop of the sample on the wax on the slide to form an assay slide, (5) maintaining the assay slide at approximately ambient temperature for a period of about 5 to about 20 minutes, and (6) determining, at the end of that period, whether when transmitting polarized light the locus of the drop on the slide displays birefringence. Birefringence at 5-20 minutes indicates the presence of anisotropic aggregates in or on the wax layer, while the absence of birefringence at that time indicates the absence of anisotropic aggregates as defined herein.
The test, as it applies to an aqueous composition of one or more excipient substances, not itself containing an exogenous chemical but intended for application to foliage of a plant in conjunction with an exogenous chemical, is as just described, except that in step (2) the composition is diluted or concentrated so that the concentration of the first excipient substance is approximately 5% to 7% by weight.
An xe2x80x9cexcipient substancexe2x80x9d as that term is used in this patent is any substance other than an exogenous chemical and water that is added to the composition. xe2x80x9cExcipient substancesxe2x80x9d include inert ingredients, although an excipient substance useful in the present invention does not have to be devoid of biological activity.
Another embodiment of the present invention is a plant treatment composition comprising (a) an exogenous chemical, and (b) a first excipient substance that is amphiphilic. As described above, the weight/weight ratio of said first excipient substance to the exogenous chemical is between about 1:3 and about 1:100, and in presence of water said composition forms anisotropic aggregates in or on a wax layer. This composition can be used in a method of treating plants, in which foliage of the plant is contacted with a biologically effective amount of a composition as described above and further comprising an aqueous diluent.
A wide variety of exogenous chemicals can be used in the compositions and methods of the present invention. A preferred class is foliar-applied exogenous chemicals, i.e. exogenous chemicals that are normally applied post-emergence to foliage of plants. A preferred subclass of foliar-applied exogenous chemicals is those that are water-soluble. By xe2x80x9cwater-solublexe2x80x9d in this context is meant having a solubility in distilled water at 25xc2x0 C. greater than about 1% by weight. Especially preferred water-soluble exogenous chemicals are salts that have an anion portion and a cation portion. In one embodiment of the invention, at least one of the anion and cation portions is biologically active and has a molecular weight of less than about 300. Particular examples of such exogenous chemicals where the cation portion is biologically active are paraquat, diquat and chlormequat. More commonly it is the anion portion that is biologically active.
Another preferred subclass of exogenous chemicals is those that exhibit systemic biological activity in the plant. Within this subclass, an especially preferred group of exogenous chemicals is N-phosphonomethylglycine and its herbicidal derivatives. N-phosphonomethylglycine, often referred to by its common name glyphosate, can be used in its acid form, but is more preferably used in the form of a salt. Any water-soluble salt of glyphosate can be used in the practice of this invention. Some preferred salts include the sodium, potassium, ammonium, mono-, di-, tri- and tetra-C1-4-alkylammonium, mono-, di- and tri-C1-4-alkanolammonium, mono-, di- and tri-C1-4-alkylsulfonium and sulfoxonium salts. The ammonium, monoisopropylammonium and trimethylsulfonium salts of glyphosate are especially preferred. Mixtures of salts can also be useful in certain situations.
A composition of the present invention comprising an exogenous chemical and a first excipient substance as described above can have a number of different physical forms. For example, the composition can further comprise water in an amount effective to make the composition a dilute aqueous composition ready for application to foliage of a plant. Such a composition typically contains about 0.02 to about 2 percent by weight of the exogenous chemical, but for some purposes can contain up to about 10 percent by weight or even more of the exogenous chemical.
Alternatively, the composition can be a shelf-stable concentrate composition comprising the exogenous chemical substance in an amount of about 10 to about 90 percent by weight. By xe2x80x9cshelf-stablexe2x80x9d in this context it is meant that the composition does not exhibit phase separation when stored at ambient temperature for a period of time dependent on the particular circumstances. Such shelf-stable concentrates can be, for example, (1) a solid composition comprising the exogenous chemical substance in an amount of about 30 to about 90 percent by weight, such as a water-soluble or water-dispersible granular formulation, or (2) a composition that further comprises a liquid diluent, wherein the composition comprises the exogenous chemical substance in an amount of about 10 to about 60 percent by weight. In this latter embodiment, it is especially preferred for the exogenous chemical substance to be water-soluble and present in an aqueous phase of the composition in an amount of about 15 to about 45 percent by weight of the composition. In particular, such a composition can be, for example, an aqueous solution concentrate or an emulsion having an oil phase. If it is an emulsion, it can more specifically be, for example, an oil-in-water emulsion, a water-in-oil emulsion, or a water-in-oil-in-water multiple emulsion. In one particular embodiment of the invention, the solid or aqueous composition further comprises a solid inorganic particulate colloidal material.
As described above, one embodiment of the invention is a sprayable composition having the property that it forms anisotropic aggregates in or on a wax layer. This composition comprises an exogenous chemical, an aqueous diluent, and a first excipient substance which is amphiphilic. In the sprayable composition, the weight/weight ratio of the first excipient substance to the exogenous chemical is between about 1:3 and about 1:100. A sprayable composition conforms to this embodiment of the invention even if the formation of anisotropic aggregates in or on a wax layer occurs only following concentration of the composition on the wax layer by evaporation of water. The term xe2x80x9cspray compositionxe2x80x9d is sometimes used herein to mean a sprayable composition.
In a related embodiment of the invention, a concentrate composition is provided which, upon dilution, dispersion or dissolution in water forms the sprayable composition just described. The concentrate composition contains a reduced amount of the aqueous diluent, or, in a particular embodiment, is a dry composition having less than about 5% water by weight. Typically a concentrate composition of the invention contains at least about 10% by weight of the exogenous chemical, preferably at least about 15%.
An alternative embodiment is a composition that does not itself comprise an exogenous chemical, but is intended for application to a plant in conjunction with or as a carrier for the application of an exogenous chemical. This composition comprises a first excipient substance as described above. Such a composition may be sprayable, in which case it also comprises an aqueous diluent, or it may be a concentrate, requiring dilution. dispersion or dissolution in water to provide a sprayable composition. Thus, this embodiment of the invention can be provided as a stand-alone product and applied to a plant, diluted as appropriate with water, simultaneously with the application of an exogenous chemical, or before or after the application of the exogenous chemical.
In all embodiments, it is believed that the first excipient substance forms supramolecular aggregates in aqueous solution or dispersion. In particular it is believed that aqueous compositions of the present invention form aggregates in aqueous solution or dispersion the majority of which are not simple micelles. xe2x80x9cMajorityxe2x80x9d means that more than 50% by weight of the first excipient substance present is in the form of complex aggregates other than simple micelles, e.g. as bilayers or multilamellar structures. Preferably, more than 75% by weight is in the form of complex aggregates other than simple micelles.
Whether or not an amphiphilic substance forms such aggregates depends on its molecular architecture. The effects of molecular architecture on supramolecular self-assembly of amphiphilic molecules, as set forth for example by J. N. Israelachvili, D. J. Mitchell and B. W. Ninham in Faraday Transactions II, Volume 72, pp. 1525-1568 (1976) and in numerous later articles and monographs, are well known and understood. An important aspect is xe2x80x9ccritical packing parameterxe2x80x9d (P) which is defined in the literature by the following equation:
P=V/lA
where V is the volume of the hydrophobic tail of the molecule, l is the effective length of the hydrophobic tail, and A is the area occupied by the hydrophilic headgroup. These dimensions can be calculated from physical measurements as described in the literature and have been published for numerous amphiphilic compounds.
It is believed that amphiphilic substances useful as the first excipient substance herein have a critical packing parameter greater than ⅓. The first excipient substance forms aggregates in aqueous solution or dispersion which preferably have at least one dimension that is greater than two times the molecular length of the first excipient substance.
In one embodiment of the invention, an aqueous composition comprises supramolecular aggregates of the first excipient substance which have an average diameter of at least 20 nm, preferably at least 30 nm.
These supramolecular aggregates can take a number of forms. In one preferred embodiment, the first excipient substance is a vesicle-forming amphiphilic substance, such as a vesicle-forming lipid, and when the substance is dispersed in water the majority (greater than 50% by weight, preferably greater than 75% by weight) of the first excipient substance is present as vesicles or liposomes. In another preferred embodiment the first excipient substance is present as bilayers or multilamellar structures which are not organized as vesicles or liposomes. Compositions of the present invention can also include, without limitation, colloidal systems such as emulsions (water/oil, oil/water, or multiple, e.g., water/oil/water), foams, microemulsions, and suspensions or dispersions of microparticulates, nanoparticulates, or microcapsules. Compositions of the invention can include more than one type of aggregate or colloidal system; examples include liposomes or vesicles dispersed in a microemulsion, and compositions having characteristics of both emulsions and suspensions, e.g. suspo-emulsions. The present invention also encompasses any formulation, which may or may not contain a significant amount of water, that on dilution in an aqueous medium forms such colloidal systems, and/or systems comprising vesicles, liposomes, bilayers or multilamellar structures, so long as the other requirements stipulated herein are met.
The weight ratio of the first excipient substance to the exogenous chemical is between about 1:3 and about 1:100. We have been surprised by the high level of biological effectiveness, specifically herbicidal effectiveness of a glyphosate composition, exhibited at such low ratios of excipient substance to exogenous chemical. Higher ratios can also be effective but are likely to be uneconomic in most situations and increase the risk of producing an antagonistic effect on effectiveness of the exogenous chemical.
Prior art exogenous chemical compositions that have included liposome-forming excipient substances have typically contained a higher percentage of the liposome-forming excipient substance than of the exogenous chemical. Compositions of the present invention, in contrast, contain less of the excipient substance than the exogenous chemical, and in some embodiments much less. This makes the compositions of the present invention much less expensive than the above-described prior art compositions. It is surprising that the enhancement of biological activity that has been observed when using the present invention can be achieved with the addition of relatively small amounts of such excipient substances.
In one embodiment of the invention the first excipient substance is a liposome-forming material that comprises an amphiphilic compound or mixture of such compounds having two hydrophobic moieties, each of which is a saturated alkyl or acyl chain having from about 8 to about 22 carbon atoms. The amphiphilic compound or mixture of such compounds having said two hydrophobic moieties with about 8 to about 22 carbon atoms constitutes from about 40 to 100 percent by weight of all amphiphilic compounds having two hydrophobic moieties present in the liposome-forming material. Preferably the liposome-forming material has a hydrophilic head group comprising a cationic group. More preferably, the cationic group is an amine or ammonium group.
In a preferred embodiment of the invention, the first excipient substance comprises a liposome-forming compound having a hydrophobic moiety comprising two saturated or unsaturated hydrocarbyl groups R1 and R2 each having about 7 to about 21 carbon atoms. A number of subclasses of such liposome-forming compounds are known.
One subclass has the formula
N+(CH2R1)(CH2R2)(R3)(R4) Zxe2x88x92xe2x80x83xe2x80x83I
wherein R3 and R4 are independently hydrogen, C1-4 alkyl or C1-4 hydroxyalkyl and Z is a suitable anion.
A second subclass has the formula
N+(R5)(R6)(R7)CH2CH(OCH2R1)CH2(OCH2R2) Zxe2x88x92xe2x80x83xe2x80x83II
wherein R5, R6 and R7 are independently hydrogen, C1-4 alkyl or C1-4 hydroxyalkyl and Z is a suitable anion.
A third subclass has the formula
N+(R5)(R6)(R7)CH2CH(OCOR1)CH2(OCOR2) Zxe2x88x92xe2x80x83xe2x80x83III
wherein R5, R6, R7 and Z are as defined above.
A fourth subclass has the formula
N+(R5)(R6)(R7)CH2CH2-PO4xe2x88x92CH2CH(OCOR1)CH2(OCOR2)xe2x80x83xe2x80x83IV
wherein R5, R6, and R7 are as defined above.
Compounds of formulas I-IV will have the indicated formulas at a pH of 4 and may have the same formulas at other pH""s as well. It should be understood, however, that compositions of the present invention are not limited to use at a pH of 4.
R1 and R2 preferably are independently saturated straight-chain alkyl groups each having about 7 to about 21 carbon atoms. Examples of suitable agriculturally acceptable anions Z include hydroxide, chloride, bromide, iodide, sulfate, phosphate and acetate.
In all of the above subclasses of liposome-forming substances, the hydrophilic moiety comprises a cationic group, specifically an amine or ammonium group. The compound as a whole is in some cases cationic (as in I, II and III) and in some cases neutral (as in IV). Where the amine group is quaternary, it behaves as a cationic group independently of pH. Where the amine group is secondary or tertiary, it behaves as a cationic group when protonated, i.e. in an acid medium, for example at a pH of 4.
In a preferred embodiment, the first excipient substance is a phospholipid selected from the group consisting of di-C8-22-alkanoylphosphatidylcholines and di-C8-22-alkanoylphosphatidylethanolamines. In a particularly preferred embodiment, the first excipient substance is a dipalmitoyl or distearoyl ester of phosphatidylcholine or a mixture thereof.
Other subclasses of liposome-forming substances having two hydrophobic chains each comprising a C7-21 hydrocarbyl group can also be used as the first excipient substance in compositions of the invention. While substances having a cationic group in the hydrophilic moiety are preferred, nonionic or anionic substances can be used if desired.
In another embodiment of the invention. the first excipient substance is an amphiphilic quaternary ammonium compound or mixture of such compounds. The hydrophobic moiety of the quaternary ammonium compound is a saturated alkyl or haloalkyl group having about 6 to about 22 carbon atoms. In this embodiment, the first excipient substance is not necessarily a liposome-forming substance, but it is believed to form aggregates in aqueous solution or dispersion as described above.
Preferred quaternary ammonium compounds (other than those which are liposome-forming and have two hydrocarbyl chains) for use as the first excipient substance in compositions of the invention have the formula
R8xe2x80x94Waxe2x80x94Xxe2x80x94Ybxe2x80x94(CH2)nxe2x80x94N+(R9)(R10)(R11) Txe2x88x92xe2x80x83xe2x80x83V
wherein R8 represents the hydrophobic moiety and is a hydrocarbyl or haloalkyl group having from about 6 to about 22 carbon atoms, W and Y are independently O or NH, a and b are independently 0 or 1 but at least one of a and b is 1, X is CO, SO or SO2, n is 2 to 4, R9, R10 and R11 are independently C1-4 alkyl, and T is a suitable anion. R8 in one particular embodiment is hydrocarbyl having about 12 to about 18 carbon atoms. R8 can also be fluorinated. In one specific embodiment, R8 is perfluorinated, and preferably has about 6 to about 12 carbon atoms. Suitable anions T include hydroxide, chloride, bromide, iodide, sulfate, phosphate and acetate. In one particularly preferred embodiment, R8 is saturated perfluoroalkyl having about 6 to about 12 carbon atoms, X is CO or SO2, Y is NH, a is 0, b is 1, n is 3, R9, R10 and R11 are methyl, and T is selected from the group consisting of chloride, bromide and iodide.
In a further embodiment of the invention, the first excipient substance is an alkylether surfactant or mixture of such surfactants having the formula
R12xe2x80x94Oxe2x80x94(CH2CH2O)n(CH(CH3)CH2O)mxe2x80x94R13xe2x80x83xe2x80x83VI
wherein R12 is an alkyl or alkenyl group having about 16 to about 22 carbon atoms, n is an average number of about 10 to about 100, m is an average number of 0 to about 5 and R13 is hydrogen or C1-4 alkyl. Preferably R12 is a saturated straight-chain alkyl group, R13 is hydrogen, m is 0 and n is from about 10 to about 40, more preferably from about 20 to about 40. Most preferably the alkylether surfactant is a polyoxyethylene cetyl or stearyl ether or mixture thereof having 20-40 moles of ethylene oxide (EO). The term xe2x80x9calkyletherxe2x80x9d as used herein should be understood to include alkenylether surfactants.
Compositions of the present invention can optionally further comprise a second excipient substance having at least one hydrophobic moiety, wherein if the second excipient substance has one hydrophobic moiety, the hydrophobic moiety is a hydrocarbyl or haloalkyl group having about 6 to about 22 carbon atoms, and wherein if the second excipient substance has a plurality of hydrophobic moieties, each such hydrophobic moiety is a hydrocarbyl or haloalkyl group having more than 2 carbon atoms, said plurality of hydrophobic moieties having a total of about 12 to about 40 carbon atoms. The second excipient substance, if present, may or may not itself be one that forms supramolecular aggregates as described above. In a particular embodiment of the invention where the first excipient substance is a liposome-forming substance of formula I, II, III or IV above, a second excipient substance is present and is a quaternary ammonium compound or mixture of such compounds. Among preferred quaternary ammonium compounds for use as the second excipient substance in this embodiment are compounds of formula V above.
In another particular embodiment of the invention where the first excipient substance is a liposome-forming substance of formula I, II, III or IV above, a second excipient substance is present and is a compound or mixture of compounds of formula
R14xe2x80x94COxe2x80x94Axe2x80x94R15 xe2x80x83xe2x80x83VII
wherein R14 is a hydrocarbyl group having about 5 to about 21 carbon atoms, R15 is a hydrocarbyl group having 1 to about 14 carbon atoms, the total number of carbon atoms in R14 and R15 is about 11 to about 27, and A is O or NH.
R14 preferably has about 11 to about 21 carbon atoms, R15 preferably has 1 to about 6 carbon atoms and A is preferably O. More preferably, the second excipient substance is a C1-4 alkyl ester of a C12-18 fatty acid, for example a propyl, isopropyl or butyl ester of a C12-18 fatty acid. Butyl stearate is an especially preferred example. The aqueous composition in embodiments comprising a compound of formula VII preferably is an emulsion comprising an oil phase that comprises said second excipient substance, for example a water-in-oil-in-water multiple emulsion or an oil-in-water emulsion. Alternatively, a second excipient substance of formula VII is associated in some way with a liposome-forming first excipient substance.
In yet another particular embodiment of the invention, the first excipient substance is an alkylether surfactant of formula VI and a second excipient substance is present and is a compound or mixture of compounds of formula VII.
In any of the above particular embodiments. the exogenous chemical and/or second excipient substance can be encapsulated within or associated with aggregates (e.g., liposomes) formed by the first excipient substance, but do not necessarily have to be so encapsulated or associated. xe2x80x9cAssociatedxe2x80x9d in this context means bound to or at least partly intercalated in some fashion in a vesicle wall, as opposed to being encapsulated. In yet another embodiment of the invention where the first excipient substance forms liposomes, the exogenous chemical and/or second excipient substance is not encapsulated in or associated with the liposomes at all. Although the present invention does not exclude the possibility of so encapsulating or associating the exogenous chemical, a presently preferred dilute sprayable liposomal composition encapsulates less than 5% by weight of the exogenous chemical that is present in the overall composition. Another dilute sprayable liposomal embodiment of the present invention has no substantial amount (i.e., less than 1% by weight) of the exogenous chemical encapsulated in the liposomes. As a droplet of such a liposomal composition dries on foliage of a plant, the proportion of the exogenous chemical that is encapsulated in the liposomes may change. Compositions of the present invention that include an exogenous chemical can be applied to foliage of plants in an amount that is effective to achieve the desired biological effect of the exogenous chemical. For example. when the exogenous chemical is a post-emergence herbicide, the composition can be applied to a plant in a herbicidally effective amount.
Without being bound by theory, it is believed that that the method and compositions of the present invention create or enlarge hydrophilic channels through the epicuticular wax of the plant cuticle, these channels being capable of accommodating the mass transfer of a water-soluble exogenous chemical into the plant, and thus transporting the exogenous chemical into the plant more rapidly or more completely than an epicuticular wax layer lacking such formation or enlargement of hydrophilic channels. Of course, certain compositions of the present invention can also enter a plant through stomata, but this generally requires a very low surface tension which is not an essential feature of the present compositions. The enhanced cuticular penetration believed to be achieved by the compositions of the present invention enhances the overall delivery and effectiveness of the exogenous chemical. Whereas an exogenous chemical such as glyphosate, formulated as an aqueous solution or dispersion with surfactants which do not have the property of forming anisotropic aggregates in or on a wax layer, normally penetrates through the epicuticular wax very slowly (e.g., in 1-4 days), a substantial portion of the exogenous chemical in compositions of the present invention penetrates much more quickly (e.g., in from about 10 minutes to a few hours, preferably in less than about 30 minutes).
Thus, methods and compositions of the invention are believed to owe their superior effectiveness at least in part to accelerated uptake into plant foliage. In conventional methods of treating plants with exogenous chemicals, in particular polar exogenous chemicals, the epicuticular wax layer presents an almost continuous barrier through which such exogenous chemicals diffuse with difficulty, even in the presence of surfactants which increase diffusive mobility but do not introduce the possibility of rapid mass transfer through hydrophilic channels.
Again without being bound by theory. it is believed that the hydrophilic channels are created within the epicuticular wax layer by the self-assembly of molecules of the first excipient substance which has a hydrophobic moiety that associates with the wax and a hydrophilic moiety that attracts water to form an aqueous continuum across the epicuticular wax layer linking up with hydrophilic pathways in the cuticle proper. A polar exogenous chemical can move by mass transfer along such an aqueous continuum to enter the plant.
Again without being bound by theory, it is believed that when the composition is present on the leaf of a plant as a droplet of aqueous solution or dispersion, in an aqueous microdomain on the cuticular surface (i.e., the aqueous region at the interface between the water droplet and the epicuticular wax). the majority (i.e., more than 50% by weight) of the aggregate-forming substance is present in a form other than a monolayer, for example as a bilayer or multilamellar (liquid crystal) structure. The aggregate-forming substances employed have several preferred characteristics that are believed to contribute to the formation of transcuticular hydrophilic channels. For instance, they have a tendency to form extended self-assembled structures in the presence of water and the kinds of waxes encountered in cuticles. Generally, materials that form non-simple (i.e., not small spherical micellar structures) aggregates in solution, such as vesicles or cylindrical, discotic, or ribbon-like micellar structures are preferred. These tend to form more complex adsorbed and absorbed layers with hydrophobic substrates than those simple micellar systems that tend to produce simple adsorbed monolayers. These substances also tend to produce lyotropic mesophases such as lamellar, hexagonal or reversed hexagonal phases in the compositions established in the aqueous microdomains in or on the cuticle.
In one embodiment of the invention, a cationic headgroup on the first excipient substance is also preferred. The cationic group is believed to enhance initial adhesion to the leaf surface, since the majority of such surfaces carry an overall negative charge. The cationic group is also believed to contribute to the hydrophilicity of channels in the epicuticular wax formed or enlarged by the method and compositions of the invention. Cationic groups, in particular amine or ammonium groups, attract water molecules which further enlarge the hydrophilic channels and thereby provide an improved pathway of entry for exogenous chemicals that are polar or water-soluble.
It is further believed that the creation or enlargement of hydrophilic channels in epicuticular wax results in the wax becoming plasticized. A further embodiment of the invention is thus a method for applying an exogenous chemical to a plant having an epicuticular wax layer, comprising (a) plasticizing the epicuticular wax layer in conjunction with (b) contacting the epicuticular wax layer with the exogenrous chemical. In this embodiment the step of plasticizing the epicuticular wax layer is accomplished by contacting the layer with an aqueous composition comprising a first excipient substance as defined above and optionally a second excipient substance as defined above. The weight ratio of the first excipient substance to the exogenous chemical is between about 1:3 and about 1:100.
Herbicidal compositions in accordance with the present invention are also useful in methods for enhancing the yield of a field crop. Such a method can comprise the steps of (a) planting a crop in a field, (b) substantially freeing the field of one or more weed species that would diminish the yield of the crop by applying to the weed species a herbicidally effective amount of a composition as described above, (c) allowing the crop to mature, and (d) harvesting the crop. Alternatively, the method can comprise the steps of (a) substantially freeing the field of one or more weed species that would diminish the yield of the crop by applying to the weed species a herbicidally effective amount of the composition, (b) planting the crop in the field, (c) allowing the crop to mature, and (d) harvesting the crop.
In one particular method in accordance with the present invention, a herbicidal composition as described above can be applied to a complex of weeds that are present in a single field, the weeds being, for example, velvetleaf, morningglory, and prickly sida. The composition is applied in a herbicidally effective amount, and provides herbicidal control of each of the weed species in the complex.
Another embodiment of the present invention is a herbicidal method, comprising contacting the foliage of a plant with a herbicidally effective amount of a composition as described above, whereby the herbicidal effectiveness of the composition on the plant to which it is applied is visibly better than the herbicidal effectiveness on that same species of plant, under substantially the same conditions, of a composition-containing a similar amount of surfactant but that does not form anisotropic aggregates. xe2x80x9cVisibly betterxe2x80x9d in this context means that the difference in herbicidal effect of the two compositions on the plants is readily noticeable to the eye of an experienced weed scientist.
Another embodiment of the present invention is a herbicidal method which can be used in a field that contains both weed and crop plants, where the crop plants are resistant to the effects of a particular herbicide at the rate that herbicide is used. The method comprises contacting the foliage of both the weeds and the crops in the field with a composition as described above. The composition will have a herbicidal effect on the weeds (i.e., it will partially or entirely kill the weeds) but it will not harm the crops. This herbicidal method applies to any combination of a selective post-emergence herbicide (e.g. 2,4-D) and a crop on which that herbicide can be used selectively to kill weeds (e.g., in the case of 2,4-D, wheat). This herbicidal method also applies to any combination of a normally non-selective post-emergence herbicide and a crop bred or genetically modified to be resistant to that herbicide. An example of a suitable combination of herbicide and herbicide-resistant crop is ROUNDUP(copyright) herbicide and ROUNDUP READY(copyright) crops, developed by Monsanto Company.
The compositions and methods of the present invention have a number of advantages. They provide enhanced biological activity of exogenous chemicals in or on plants in comparison with prior formulations, either in terms of greater ultimate biological effect. or obtaining an equivalent biological effect while using a reduced application rate of exogenous chemical. Certain herbicide formulations of the present invention can avoid antagonism that has been observed in some prior art herbicide formulations, and can minimize quick production of necrotic lesions on leaves that in some situations hinder overall translocation of herbicide in the plant. Certain herbicide compositions of the invention modify the spectrum of activity of the herbicide across a range of plant species. For example, certain formulations of the present invention containing glyphosate can provide good herbicidal activity against broadleaf weeds while not losing any herbicidal effectiveness on narrowleaf weeds. Others can enhance herbicidal effectiveness on narrowleaf weeds to a greater extent than on broadleaf weeds. Still others can have enhanced effectiveness which is specific to a narrow range of species or even a single species.
Another advantage of the present invention is that it employs relatively small amounts of the first and second excipient substances in relation to the amount of exogenous chemical employed. This makes the compositions and methods of the present invention relatively inexpensive, and also tends to reduce instability problems in specific compositions where one or both excipient substances are physically incompatible with the exogenous chemical (e.g., alkylether surfactants in solutions of high ionic strength, such as concentrated glyphosate salt solutions).
Even at the low concentrations of the excipient substances used in the present invention, there may be limits on the maximum concentration of exogenous chemical that can be used without causing compatibility problems (e.g., separation of the composition into discrete layers). In some preferred embodiments of the invention, composition stability at high loadings of exogenous chemical is maintained by adding other ingredients such as, for example, colloidal particulates. Some compositions of the present invention exhibit enhanced biological activity and have a higher loading of exogenous chemical than possible in prior art compositions.
Further, compositions of the present invention are less sensitive in some instances to environmental conditions such as relative humidity at the time of application to the plant. Also, the present invention allows the use of smaller amounts of herbicides or other pesticides, while still obtaining the required degree of control of weeds or other undesired organisms.
When the phrase xe2x80x9canisotropic aggregates in or on a wax layerxe2x80x9d is used herein, it relates to determinations made by the following test procedure. We have found this test to predict with a high degree of reliability whether a composition comprising water and an exogenous chemical, or a composition comprising water which is to be used in conjunction with an exogenous chemical, will show enhanced biological effectiveness when applied to foliage of plants. Modifications can be made to the test; however a procedure modified in some major respect will not necessarily give the same results and will not necessarily predict enhanced effectiveness as reliably as the procedure described here.
The first stage in the procedure is to prepare a wax-coated slide. We have found a preferred wax for the purpose to be a blend of carnauba wax and beeswax in a weight/weight ratio of approximately 10:1. A clear wax mixture is prepared consisting of 5% carnauba wax and 0.5% beeswax in isopropanol, and is maintained at a temperature of approximately 82xc2x0 C. The end of a glass 2.4 cmxc3x977.2 cm microscope slide is immersed perpendicularly in the wax mixture to a depth of approximately one-third of the length of the slide. After 10 to 15 seconds, the slide is very slowly and steadily withdrawn from the wax mixture and allowed to cool. leaving a wax layer deposited on both faces of the slide.
Visual examination of the slide can give a preliminary indication of the thickness and uniformity of the wax coating. If imperfections are evident the slide is rejected. If the slide shows no obvious imperfections, the wax coating is carefully removed from one face of the slide by wiping with acetone. Further evaluation of the acceptability of the wax-coated slide for the test is done by examining the slide under a microscope. The slide is selected for use in the test if, on microscopic examination using a 4.9xc3x97 objective, the wax coating is uniformly thick and there is uniform density of wax particles across the slide. Preference is for a coating that has few observable wax particles and exhibits a very dark field when examined under polarized light.
The next stage in the procedure is to conduct the test. For this purpose, samples of an exogenous chemical composition to be tested are diluted, if necessary, to 15% to 20% by weight of the exogenous chemical. In the case of glyphosate, the desired concentration in a composition sample is 15% to 20% acid equivalent (a.e.). Samples of reference compositions are also prepared; in the case of glyphosate, Formulations B and J as defined in the Examples herein are appropriate.
For a composition of a first excipient substance not containing an exogenous chemical but to be applied in conjunction with an exogenous chemical, the desired concentration is approximately 5% to 7% by weight of the first excipient substance.
The following instrumentation, or equivalent, items are required or useful:
Nikon SMZ-10A stereoscopic microscope equipped for polarized light observation, photomicrography, and video observation and recording.
3CCD MTI camera.
Diagnostic Instruments 150 IL-PS power supply.
Sony Trinitron color video monitor, model PVM-1353MD.
Mitsubishi time-lapse video cassette recorder, model HS-S5600.
Hewlett Packard Pavillion 7270 computer, with Windows 95 and Image-Pro Plus version 2.0 electronic imaging program installed.
Hewlett Packard Deskjet 870Cse printer.
A wax-coated slide, prepared and selected as described above, is positioned on the microscope stage, with the system set-to provide transmitted light, both straight and polarized. A 1 xcexcl drop of the sample to be tested is applied to the wax surface using a thoroughly cleaned 1 xcexcl Hamilton syringe. This and subsequent operations are followed through the microscope at 4.9xc3x97 objective. Duplicate or triplicate tests are done for each composition. Numerous tests can be conducted simultaneously on a single slide. Progression of change in the microscopic appearance of the sample is observed through the microscope and recorded at designated time intervals. We have found useful intervals to be 1 minute, 10 minutes, 2 hours and  greater than 24 hours after application of the drop to the wax surface. Observations can also be made at intermediate times to capture possible significant transitions occurring at such times.
The temperature of the wax layer tends to increase with prolonged exposure to the microscope light. In many cases we have found this does not significantly interfere with the results obtained. However, in some cases temperature does affect the outcome of the test and in such cases it is preferred to illuminate the sample only for the short periods necessary to make observations, so that the temperature of the wax layer remains close to ambient temperature. An example of a composition of the invention where it is believed to be important to keep temperature close to ambient is one containing a fatty acid ester such as butyl stearate.
At dark field (polarized light) the wax layer is observed for birefringence, and at light field the character of the drop surface is observed, at each time interval. The following records are made:
birefringence (yes/no);
time of initial appearance of birefringence;
character of the birefringence,
appearance of drop surface as composition xe2x80x9cdriesxe2x80x9d;
degree of spread of the drop;
effects of temperature (warming of the slide) if any;
other noticeable changes.
Optionally, images are recorded at significant times using the 3CCD MTI camera and the Image-Pro Plus program as documentation of observed changes. Tests may if desired also be recorded on video, especially during the first 15 minutes. In addition to images captured using 4.9xc3x97 objective, overall-field views using 0.75xc3x97 objective can be recorded to provide clear comparisons of different samples tested on the same slide.
A particularly useful parameter for predicting enhanced effectiveness is the observation of birefringence (yes/no) 5-20 minutes after deposition of the test drop on the wax-coated slide. We have found 10-15 minutes after deposition to be an especially suitable time for observation of this parameter. The following results for oil-in-water emulsion compositions comprising glyphosate IPA salt, butyl stearate and alkylether surfactants are typical of those obtained. Each of compositions WCS-1 to WCS-5 contained 15% w/w glyphosate a.e., 0.5% w/w butyl stearate and 5% w/w alkylether surfactant. Formulations B and J are commercial standard compositions of glyphosate defined in the Examples section later herein, and were diluted to 15% glyphosate a.e. for the test.
It will be noted that where the hydrophobic moiety of the alkylether was a C11 (WCS-5) or C12 (WCS-4) hydrocarbyl group, the composition did not show anisotropic properties in the form of birefringence 10 minutes after application to the wax-coated slide. However, where the hydrophobic moiety had a carbon chain length of 16 to 18 (WCS-1 to WCS-3), birefringence was evident, indicating the presence of anisotropic aggregates in or on the wax layer. The intensity of birefringence was greatest with WCS-1 (containing steareth-20), followed by WCS-2 (containing ceteareth-27) and then WCS-3 (oleth-20).
Tests of alkylether compositions, as evidenced in Examples herein, have shown that in general those containing alkylethers of hydrophobe carbon chain length 16 or greater show greater biological effectiveness than those having a shorter hydrophobe. In general greater biological effectiveness has been obtained where the hydrophobe is saturated (as, for example, in steareth-20 and ceteareth-27) than where it is unsaturated 8 (as, for example, in oleth-20).
The following compositions were made containing 15% glyphosate a.e. and 5% alkylether surfactant, but no butyl stearate. In WCS-10 the surfactant was steareth-10, in 11 WCS-1 1 oleth-10 and in WCS-12 steareth-8 (laboratory sample from Sigma).
The property of forming anisotropic aggregates as determined by this test appears to require, on a C16-18 straight-chain alcohol, a minimum of about 10 moles of ethylene oxide (EO). Where the alcohol is oleyl, an EO chain of 10 units is already too short, but where the alcohol is stearyl, even as short an EO chain as 8 units appears to suffice. It should be noted, however, that the steareth-8 used in composition WCS-12 was obtained as a laboratory sample and is likely chemically purer than the commercial surfactants used in other compositions. Commercial grade steareth-8 will not necessarily give the same result.
As further evidence of the usefulness of the present anisotropy test in predicting biological effectiveness of exogenous chemical compositions, compositions WCS-6, WCS-7 and WCS-8 were prepared, each containing 30% glyphosate a.e. by weight, and were then diluted to 15% glyphosate a.e. for the test. All contained soybean lecithin (45% phospholipid, Avanti) and were prepared by process (v) as detailed in the Examples herein. Composition WCS-6, before dilution, contained 5% lecithin, 5% Fluorad FC-754 and 0.75% Ethomeen T/25. Composition WCS-7, before dilution, contained 2% lecithin and 2% Fluorad FC-754. Composition WCS-8, before dilution, contained 2% lecithin and 0.75% Ethomeen T/25. In addition. Composition WCS-9 was prepared containing 15% glyphosate a.e. and 5% soybean lecithin (45% phospholipid, Avanti). The following results were obtained.
As evidenced in the Examples herein, enhanced biological effectiveness is a feature of compositions containing lecithin as the first excipient substance and Fluorad FC-754 as the second excipient substance. In the absence of Fluorad FC-754 or like material, lecithin, either alone or together with a tertiary alkylamine surfactant such as Ethomeen T/25 or MON 0818, does not consistently generate the desired enhancement.
In a further demonstration of the usefulness of the present anisotropy test, compositions WCS-13 and WCS-14 were prepared, each containing 20% glyphosate a.e. by weight, and were then diluted to 15% glyphosate a.e. for the test. Both contained soybean lecithin (45% phospholipid, Avanti). Composition WCS-13 was made by process (x) as described in the Examples herein and, before dilution, contained 6% lecithin, 6% Ethomeen T/25 and 1.5% butyl stearate. Composition WCS-14 was identical except that it contained no butyl stearate. Particular care was taken in this study to avoid excessive warming of the wax-coated slide by prolonged illumination. The following results were obtained.
The addition of a small quantity of butyl stearate was thus sufficient to confer, on a glyphosate+lecithin+Ethomeen T/25 composition, the property of forming anisotropic aggregates in or on a wax layer. The Examples herein illustrate the unexpected enhancement of biological effectiveness observed when an exogenous chemical is formulated with lecithin and a fatty acid ester such as butyl stearate.
Thus where, for reasons of economy, compatibility with the exogenous chemical, or other. considerations it is desired to provide an exogenous chemical composition having a relatively low content of excipient substances (for example a weight ratio of each excipient substance to exogenous chemical of about 1:3 or less), the anisotropy test provided here is an in vitro assay method which can be used to identify biologically effective compositions in advance of extensive testing in vivo.
The in vitro assay method just described, together with modifications thereof that will be readily apparent to those of skill in the art, is a further embodiment of the present invention.
Examples of exogenous chemical substances that can be included in compositions of the present invention include, but are not limited to, chemical pesticides (such as herbicides, algicides, fungicides, bactericides, viricides, insecticides, aphicides, miticides, nematicides, molluscicides and the like), plant growth regulators, fertilizers and nutrients, gametocides, defoliants, desiccants, mixtures thereof and the like. In one embodiment of the invention, the exogenous chemical is polar.
A preferred group of exogenous chemicals are those that are normally applied post-emergence to the foliage of plants, i.e. foliar-applied exogenous chemicals.
Some exogenous chemicals useful in the present invention are water-soluble, for example salts that comprise biologically active ions, and also comprise counterions, which may be biologically inert or relatively inactive. A particularly preferred group of these water-soluble exogenous chemicals or their biologically active ions or moieties are systemic in plants, that is, they are to some extent translocated from the point of entry in the foliage to other parts of the plant where they can exert their desired biological effect. Especially preferred among these are herbicides, plant growth regulators and nematicides, particularly those that have a molecular weight, excluding counterions, of less than about 300. More especially preferred among these are exogenous chemical compounds having one or more functional groups selected from amine, carboxylate, phosphonate and phosphinate groups.
Among such compounds, an even more preferred group are herbicidal or plant growth regulating exogenous chemical compounds having at least one of each of amine, carboxylate, and either phosphonate or phosphinate functional groups. Salts of N-phosphonomethylglycine are examples of this group of exogenous chemicals. Further examples include salts of glufosinate. for instance the ammonium salt (ammonium DL-homoalanin-4-yl (methyl) phosphinate).
Another preferred group of exogenous chemicals which can be applied by the method of the invention are nematicides such as those disclosed in U.S. Pat. No. 5,389,680, the disclosure of which is incorporated herein by reference. Preferred nematicides of this group are salts of 3,4,4-trifluoro-3-butenoic acid or of N-(3,4,4-trifluoro-1-oxo-3-butenyl) glycine.
Exogenous chemicals which can usefully be applied by the method of the present invention are normally, but not exclusively, those which are expected to have a beneficial effect on the overall growth or yield of desired plants such as crops, or a deleterious or lethal effect on the growth of undesirable plants such as weeds. The method of the present invention is particularly useful for herbicides, especially those that are normally applied post-emergence to the foliage of unwanted vegetation.
Herbicides which can be applied by the method of the present invention include but are not limited to any listed in standard reference works such as the xe2x80x9cHerbicide Handbook,xe2x80x9d Weed Science Society of America, 1994, 7th Edition, or the xe2x80x9cFarm Chemicals Handbook,xe2x80x9d Meister Publishing Company, 1997 Edition. Illustratively these herbicides include acetanilides such as acetochlor, alachlor and metolachlor, aminotriazole, asulam, bentazon, bialaphos, bipyridyls such as paraquat, bromacil, cyclohexenones such as clethodim and sethoxydim, dicamba, diflufenican, dinitroanilines such as pendimethalin, diphenylethers such as acifluorfen, fomesafen and oxyfluorfen, fatty acids such as C9-10 fatty acids, fosamine, flupoxam, glufosinate, glyphosate, hydroxybenzonitriles such as bromoxynil, imidazolinones such as imazaquin and imazethapyr, isoxaben, norflurazon, phenoxies such as 2,4-D, phenoxypropionates such as diclofop, fluazifop and quizalofop, picloram, propanil, substituted ureas such as fluometuron and isoproturon, sulfonylureas such as chlorimuron, chlorsulfuron, halosulfuron, metsulfuron, primisulfuron, sulfometuron and sulfosulfuron, thiocarbamates such as triallate. triazines such as atrazine and metribuzin, and triclopyr. Herbicidally active derivatives of any known herbicide are also within the scope of the present invention. A herbicidally active derivative is any compound which is a minor structural modification, most commonly but not restrictively a salt or ester, of a known herbicide. These compounds retain the essential activity of the parent herbicide, but may not necessarily have a potency equal to that of the parent herbicide. These compounds may convert to the parent herbicide before or after they enter the treated plant. Mixtures or coformulations of a herbicide with other ingredients. or of more than one herbicide, may likewise be employed.
An especially preferred herbicide is N-phosphonomethylglycine (glyphosate), a salt, adduct or ester thereof, or a compound which is converted to glyphosate in plant tissues or which otherwise provides glyphosate ion. Glyphosate salts that can be used according to this invention include but are not restricted to alkali metal, for example sodium and potassium, salts; ammonium salt; alkylamine, for example dimethylamine and isopropylamine, salts; alkanolamine, for example ethanolamine, salts; alkylsulfonium, for example trimethylsulfonium, salts; sulfoxonium salts; and mixtures thereof. The herbicidal compositions sold by Monsanto Company as ROUNDUP(copyright) and ACCORD(copyright) contain the monoisopropylamine (IPA) salt of N-phosphonomethylglycine. The herbicidal compositions sold by Monsanto Company as ROUNDUP(copyright) Dry and RIVAL(copyright) (contain the monoammonium salt of N-phosphonomethylglycine. The herbicidal composition sold by Monsanto Company as ROUNDUP(copyright) Geoforce contains the monosodium salt of N-phosphonomethylglycine. The herbicidal composition sold by Zeneca as TOUCHDOWN(copyright) contains the trimethylsulfonium salt of N-phosphonomethylglycine. The herbicidal properties of N-phosphonomethylglycine and its derivatives were first discovered by Franz, then disclosed and patented in U.S. Pat. No. 3,799,758, issued Mar. 26, 1974. A number of herbicidal salts of N-phosphonomethylglycine were patented by Franz in U.S. Pat. No. 4,405,531, issued Sep. 20, 1983. The disclosures of both of these patents are hereby incorporated by reference.
Because the commercially most important herbicidal derivatives of N-phosphonomethylglycine are certain salts thereof, the glyphosate compositions useful in the present invention will be described in more detail with respect to such salts. These salts are. well known and include ammonium, IPA, alkali metal (such as the mono-, di-, and trisodium salts, and the mono-, di-, and tripotassium salts), and trimethylsulfonium salts. Salts of N-phosphonomethylglycine are commercially significant in part because they are water soluble. The salts listed immediately above are highly water soluble, thereby allowing for highly concentrated solutions that can be diluted at the site of use. In accordance with the method of this invention as it pertains to glyphosate herbicide, an aqueous solution containing a herbicidally effective amount of glyphosate and other components in accordance with the invention is applied to foliage of plants. Such an aqueous solution can be obtained by dilution of a concentrated glyphosate salt solution with water, or dissolution or dispersion in water of a dry (e.g. granular, powder, tablet or briquette) glyphosate formulation.
Exogenous chemicals should be applied to plants at a rate sufficient to give the desired biological effect. These application rates are usually expressed as amount of exogenous chemical per unit area treated, e.g. grams per hectare (g/ha). What constitutes a xe2x80x9cdesired effectxe2x80x9d varies according to the standards and practice of those who investigate, develop, market and use a specific class of exogenous chemicals. For example, in the case of a herbicide, the amount applied per unit area to give 85% control of a plant species as measured by growth reduction or mortality is often used to define a commercially effective rate.
Herbicidal effectiveness is one of the biological effects that can be enhanced through this invention. xe2x80x9cHerbicidal effectiveness,xe2x80x9d as used herein, refers to any observable measure of control of plant growth, which can include one or more of the actions of (1) killing, (2) inhibiting growth, reproduction or proliferation, and (3) removing, destroying, or otherwise diminishing the occurrence and activity of plants.
The herbicidal effectiveness data set forth herein report xe2x80x9cinhibitionxe2x80x9d as a percentage following a standard procedure in the art which reflects a visual assessment of plant mortality and growth reduction by comparison with untreated plants, made by technicians specially trained to make and record such observations. In all cases. a single technician makes all assessments of percent inhibition within any one experiment or trial. Such measurements are relied upon and regularly reported by Monsanto Company in the course of its herbicide business.
The selection of application rates that are biologically effective for a specific exogenous chemical is within the skill of the ordinary agricultural scientist. Those of skill in the art will likewise recognize that individual plant conditions, weather and growing conditions, as well as the specific exogenous chemical and formulation thereof selected, will affect the efficacy achieved in practicing this invention. Useful application rates for exogenous chemicals employed can depend upon all of the above conditions. With respect to the use of the method of this invention for glyphosate herbicide, much information is known about appropriate application rates. Over two decades of glyphosate use and published studies relating to such use have provided abundant information from which a weed control practitioner can select glyphosate application rates that are herbicidally effective on particular species at particular growth stages in particular environmental conditions.
Herbicidal compositions of glyphosate or derivatives thereof are used to control a very wide variety of plants worldwide. Such compositions can be applied to a plant in a herbicidally effective amount, and can effectively control one or more plant species of one or more of the following genera without restriction: Abutilon, Amaranthus, Artemisia, Asclepias, Avena, Axonopus, Borreria, Brachiaria, Brassica, Bromus, Chenopodium, Cirsium, Conmmelina, Convolvulus, Cynodon, Cyperus, Digitaria, Echinochloa, Eleusine, Elymus, Equisetum, Erodium, Helianthus, Imperata, Ipomoea, Kochia, Lolium, Malva, Oryza, Ottochloa, Panicum, Paspalum, Phalaris, Phragmites, Polygonum, Portulaca, Pteridium, Pueraria, Rubus, Salsola, Setaria, Sida, Sinapis, Sorghum, Triticum, Typha, Ulex, Xanthium, and Zea.
Particularly important species for which glyphosate compositions are used are exemplified without limitation by the following:
Annual broadleaves:
velvetleaf (Abutilon theophrasti)
pigweed (Amaranthus spp.)
buttonweed (Borreria spp.)
oilseed rape, canola, indian mustard, etc. (Brassica spp.)
comrelina (Commelina spp.)
filaree (Erodium spp.)
sunflower (Helianthus spp.)
momingglory (Ipomoea spp.)
kochia (Kochia scoparia)
mallow (Malva spp.)
wild buckwheat, smartweed, etc. (Polygonum spp.)
purslane (Portulaca spp.)
russian thistle (Salsola spp.)
sida (Sida spp.)
wild mustard (Sinapis arvensis)
cocklebur (Xanthium spp.)
Annual narrowleaves:
wild oat (Avena fatua)
carpetgrass (Axonopus spp.)
downy brome (Bromus tectorurn)
crabgrass (Digitaria spp.)
barnyardgrass (Echinochloa crus-galli)
goosegrass (Eleusine indica)
annual ryegrass (Lolium multiflorum)
rice (Oryza sativa)
ottochloa (Ottochloa nodosa)
bahiagrass (Paspalum notatum)
canarygrass (Phalaris spp.)
foxtail (Setaria spp.)
wheat (Triticurn aestivum)
corn (Zea mays)
Perennial broadleaves:
mugwort (Artemisia spp.)
milkweed (Asclepias spp.)
canada thistle (Cirsium arvense)
field bindweed (Convolvulus arvensis)
kudzu (Pueraria spp.)
Perennial narrowleaves:
brachiaria (Brachiaria spp.)
bermudagrass (Cynodon dactylon)
yellow nutsedge (Cyperus esculentus)
purple nutsedge (C. rotundus)
quackgrass (Elymus repens)
lalang (Imperata cylindrica)
perennial ryegrass (Lolium perenne)
guineagrass (Panicum maximum)
dallisgrass (Paspalum dilatatum)
reed (Phragmites spp.)
johnsongrass (Sorghum halepense)
cattail (Typha spp.)
Other perennials:
horsetail (Equisetum spp.)
bracken (Pteridium aquilinum)
blackberry (Rubus spp.)
gorse (Ulex europaeus)
Thus, the method of the present invention, as it pertains to glyphosate herbicide, can be useful on any of the above species.
Effectiveness in greenhouse tests, usually at exogenous chemical rates lower than those normally effective in the field, is a proven indicator of consistency of field performance at normal use rates. However, even the most promising composition sometimes fails to exhibit enhanced performance in individual greenhouse tests. As illustrated in the Examples herein, a pattern of enhancement emerges over a series of greenhouse tests; when such a pattern is identified this is strong evidence of biological enhancement that will be useful in the field.
Aggregate-forming substances useful as the first excipient substance in compositions of the present invention include a wide variety of amphiphilic materials, of which three classes are preferred.
The first preferred class of aggregate-forming substances can be defined as amphiphilic liposome-forming substances. These include various lipids of synthetic, animal, or plant origin, including phospholipids, ceramides, sphingolipids, dialkyl surfactants, and polymeric surfactants. A variety of these materials are known to those skilled in the art, and are commercially available. Lecithins are particularly rich in phospholipids and can be derived from a number of plant and animal sources. Soybean lecithin is one particular example of a relatively inexpensive commercially available material that includes such substances.
Many other substances have been described which can be used to form liposomes; the present invention includes compositions comprising any such liposome-forming substances, so long as other requirements set out above are met, and use of such compositions for enhancing biological effectiveness of exogenous chemicals applied to foliage of plants. For example, U.S. Pat. No. 5,580,859, incorporated here by reference, discloses liposome-forming substances having a cationic group, including N-(2,3-di-(9-(Z)-octadecenyloxy))-prop-1-yl-N,N,N-trimethylammonium chloride (DOTMA) and 1,2-bis(oleoyloxy)-3-(trimethylammonio)propane (DOTAP). Liposome-forming substances which are not themselves cationic, but do contain a cationic group as part of the hydrophilic moiety, include for example dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE). Liposome-forming substances that do not contain a cationic group include dioleoylphosphatidylglycerol (DOPG). Any of these liposome-forming substances can be used with or without the addition of cholesterol.
These substances contain portions that are hydrophilic and hydrophobic within the same molecule. They have the ability to self-assemble in aqueous solution or dispersion into structures that are more complex than simple micelles. The nature of the aggregate that will be formed can be related to the critical packing parameter P by the following equation:
P=V/lA
where V is the volume of the hydrophobic tail of the molecule, l is the effective length of the hydrophobic tail, and A is the area occupied by the hydrophilic headgroup in the surface of the aggregate. The most probable self-assembled structures are spherical micelles when P is less than ⅓, rodlike micelles when P is between ⅓ and xc2xd, lamellar when P is between 1 and xc2xd, and inverse structures when P is greater than 1. The preferred materials in the present invention have P greater than ⅓.
Cationic liposome-forming substances having a hydrophobic moiety comprising two hydrocarbyl chains are accompanied by a counterion (anion), identified as Z in formulas I, II and III above. Any suitable anion can be used, including agriculturally acceptable anions such as hydroxide. chloride, bromide, iodide, sulfate, phosphate and acetate. In a specific embodiment where the exogenous chemical has a biologically active anion, that anion can serve as the counterion for the liposome-forming substance. For example, glyphosate can be used in its acid form together with the hydroxide of a cationic liposome-forming substance such as a compound of formula I.
Compounds of formula I known in the art to be liposome-forming include distearyldimethylammonium chloride and bromide (also known in the art as DODAC and DODAB respectively). Compounds of formula II known in the art to be liposome-forming include DOTMA referenced above and dimyristooxypropyldimethylhydroxyethylammonium bromide (DMRIE). Compounds of formula III known in the art to be liposome-forming include dioleoyloxy-3-(dimethylammonio)propane (DODAP) and DOTAP referenced above. Compounds of formula IV known in the art to be liposome-forming include DOPC and DOPE, both referenced above.
In many liposome-forming substances known in the art, the hydrophobic hydrocarbyl chains are unsaturated, having one or more double bonds. Particularly commonly used in the pharmaceutical art are dioleyl or dioleoyl compounds. A potential problem with these is that in an oxidizing environment they become oxidized at the site of the double bond. This can be inhibited by including in the formulation an antioxidant such as ascorbic acid. Alternatively the problem can be avoided by use of liposome-forming substances wherein a high proportion of the hydrophobic hydrocarbyl chains are fully saturated. Thus in a preferred embodiment of the invention, R1 and R2 in formulas I-IV are independently saturated straight-chain alkyl groups. Particularly preferred compositions use liposome-forming substances in which R1 and R2 are both palmityl (cetyl) or palmitoyl or, alternatively, are both stearyl or stearoyl groups.
Phospholipids, because of their low cost and favorable environmental properties, are particularly favored among liposome-forming substances in the method and compositions of the invention. Vegetable lecithins, such as soybean lecithin, have successfully been used in accordance with the invention. The phospholipid content of the lecithin product can range from about 10% to close to 100%. While acceptable results have been obtained with crude lecithin (10-20% phospholipid), it is generally preferred to use lecithin that is at least partially de-oiled, so that the phospholipid content is in the region of about 45% or more. Higher grades. such as 95%, provide excellent results but the much higher cost is unlikely to be justified for most applications.
The phospholipid component of lecithin, or any phospholipid composition used in the present invention, may comprise one or more phosphatides of natural or synthetic origin. Each of these phosphatides is generally a phosphoric ester that on hydrolysis yields phosphoric acid, fatty acid(s), polyhydric alcohol and, typically, a nitrogenous base. A phosphatide component may be present in a partially hydrolyzed form, e.g. as phosphatidic acid. Suitable phosphatides include, without limitation, phosphatidylcholine, hydrogenated phosphatidylcholine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, phosphatidylethanolamine, N-acyl phosphatidylethanolamine, and mixtures of any of these.
In vegetable lecithins a high proportion of the hydrophobic hydrocarbyl chains of the phospholipid compounds are typically unsaturated. One preferred embodiment of compositions in accordance with the present invention comprises both saturated phospholipid and unsaturated phospholipid, with the weight ratio of saturated phospholipid to unsaturated phospholipid being greater than about 1:2. In various particularly preferred embodiments, (1) at least 50% by weight of the phospholipids are di-C12-22-saturated alkanoyl phospholipid, (2) at least 50% by weight of the phospholipids are di-C16-18-saturated alkanoyl phospholipid, (3) at least 50% by weight of the phospholipids are distearoyl phospholipid, (4) at least 50% by weight of the phospholipids are dipalmitoyl phospholipid, or (5) at least 50% by weight of the phospholipids are distearoyl phosphatidylcholine. dipalmitoyl phosphatidylcholine, or a mixture thereof. Higher proportions of saturated alkanoyl phospholipids are generally found in lecithins of animal origin, such as for example egg yolk lecithin, than in vegetable lecithins.
Phospholipids are known to be chemically unstable, at least in acid media, where they tend to degrade to their lyso-counterparts. Thus where phospholipids rather than more stable liposome-forming substances are used, it is usually preferable to adjust the pH of the composition upward. In the case of glyphosate compositions, the pH of a composition based on a mono-salt such as the monoisopropylammonium (IPA) salt is typically around 5 or lower. When phospholipids are used as the first excipient substance in a glyphosate composition of the invention, it will therefore be preferable to raise the pH of the composition, for example to around 7. Any convenient base can be used for this purpose; it will often be most convenient to use the same base as used in the glyphosate salt, for example isopropylamine in the case of glyphosate IPA salt.
Amphiphilic compounds useful as the first excipient substance herein are not limited to those having two hydrophobic hydrocarbyl groups such as the compounds of formulas I to IV. The second preferred class of aggregate-forming substances useful in the invention are cationic surfactant compounds having formula V above. In compounds of formula V, R8 unless perfluorinated preferably has from about 12 to about 18 carbon atoms. R8 is preferably perfluorinated, in which case it preferably has from about 6 to about 12 carbon atoms. Preferably n is 3. R9 groups are preferably methyl.
Sulfonylamino compounds of formula V are especially preferred. Suitable examples include 3-(((heptadecafluorooctyl)sulfonyl)amino)-N,N,N-trimethyl-1-propaminium iodide, available for example as Fluorad FC-135 from 3M Company, and the corresponding chloride. It is believed that Fluorad FC-754 of 3M Company is the corresponding chloride.
Fluoro-organic surfactants such as the cationic types falling within formula V belong to a functional category of surfactants known in the art as xe2x80x9csuperspreadersxe2x80x9d or xe2x80x9csuperwettersxe2x80x9d. As a class xe2x80x9csuperspreadersxe2x80x9d or xe2x80x9csuperwettersxe2x80x9d are very effective in reducing surface tension of aqueous compositions containing relatively low concentrations of these surfactants. In many applications fluoro-organic surfactants can substitute for organosilicone surfactants which are likewise xe2x80x9csuperspreadersxe2x80x9d or xe2x80x9csuperwettersxe2x80x9d. An example is found in European patent application 0 394 211 which discloses that either organosilicone or fluoro-organic surfactants can be used interchangeably in solid granular formulations of pesticides to improve dissolution rate.
Two major problems have limited interest in xe2x80x9csuperspreadersxe2x80x9d and xe2x80x9csuperwettersxe2x80x9d by formulators of exogenous chemicals such as pesticides. The first is high unit cost. The second is that although surfactants of this functional category can enhance performance of an exogenous chemical on some species, for example by assisting penetration of the exogenous chemical into the interior of leaves via stomata, they can be antagonistic, sometimes severely so, to performance of the same exogenous chemical on other species.
Surprisingly, a subclass of fluoro-organic surfactants has now been found to be essentially non-antagonistic at concentrations which nevertheless provide useful adjuvant effects. This subclass comprises cationic fluoro-organic surfactants of formula V and others having a property profile in common with those of formula V. The lack of antagonism makes this subclass very different from other fluoro-organic xe2x80x9csuperspreadersxe2x80x9d or xe2x80x9csuperwettersxe2x80x9d. Further, it has been found that these non-antagonistic fluoro-organic surfactants can be useful at concentrations low enough to be cost-effective. Data in the Examples herein for compositions comprising Fluorad FC-135 or Fluorad FC-754 illustrate the unexpected properties of this subclass.
Derivatives of Fluorad FC-754, herein described as xe2x80x9cFC-acetatexe2x80x9d and xe2x80x9cFC-salicylate,xe2x80x9d have been prepared by the following procedure. (1) The solvent in a sample of Fluorad FC-754 is gently evaporated off by heating in a glass beaker at 70-80xc2x0 C., to leave a solid residue. (2) The solid residue is allowed to cool to room temperature. (3) A 1 g aliquot of the residue is placed in a centrifuge tube and dissolved in 5 ml isopropanol. (4) A saturated solution of potassium hydroxide (KOH) is prepared in isopropanol. (5) This solution is added drop by drop to the solution of FC-754 residue; this results in formation of a precipitate and addition of KOH solution continues until no further precipitate forms. (6) The tube is centrifuged at 4000 rpm for 5 minutes. (7) More KOH solution is added to check if precipitation is complete; if not, the tube is centrifuged again. (8) The supernatant is decanted into another glass tube. (9) A saturated solution of acetic acid (or salicylic acid) is prepared in isopropanol. (10) This solution is added to the supernatant in an amount sufficient to lower pH to 7. (11) Isopropanol is evaporated from this neutralized solution by heating at 60xc2x0 C. until completely dry. (12) The residue (either the acetate or salicylate salt) is dissolved in a suitable amount of water and is then ready for use.
The third preferred class of aggregate-forming substance useful as the first excipient substance according to the present invention is a long-chain alkylether surfactant having the formula VI above. R12 can be branched or unbranched, saturated or unsaturated. R12 is preferably straight chain saturated C16 alkyl (cetyl) or straight chain saturated C18 alkyl (stearyl). In preferred alkylethers m is 0, n is an average number from about 20 to about 40 and R13 is preferably hydrogen. Among especially preferred alkylether surfactants are those identified in the International Cosmetic Ingredient Directory as ceteth-20, ceteareth-20, ceteareth-27, steareth-20 and steareth-30.
Of the classes of aggregate-forming substance useful as the first excipient substance, not all give rise to anisotropic aggregates in or on a wax layer, as required by the present invention, when used as the sole excipient substance in the composition at a weight ratio of 1:3 to 1:100 with the exogenous chemical. Many compounds of formulas V and VI are sufficient in the absence of a second excipient substance, but in general the liposome-forming substances of formulas I to IV require the presence of a second excipient substance to exhibit the required anisotropic behavior. However, even in the presence of a first excipient substance of formulas V or VI, there may be advantages in also including a second excipient substance as herein defined.
The second excipient substance has one or more hydrophobic moieties. If there is only one hydrophobic moiety, it is a hydrocarbyl or haloalkyl group having about 6 to about 22 carbon atoms. If there is more than one hydrophobic moiety, each such moiety is a hydrocarbyl or haloalkyl group having more than 2 carbon atoms, and the total number of carbon atoms in the hydrophobic moieties is about 12 to about 40.
One class of second excipient substance useful in the present invention is quaternary ammonium compounds. Among quaternary ammonium compounds that may be used are compounds of formula
N+(R16)(R17)(R18)(R19) Qxe2x88x92xe2x80x83xe2x80x83VIII
where R16, R17, R18 and R19 are independently C3-6 alkyl groups and Q is a suitable anion, such as for example hydroxide, chloride, bromide, iodide, sulfate, phosphate or acetate. In preferred compounds of formula VIII all R groups are the same. Particularly preferred compounds of formula VIII are tetrabutylammonium salts. Where the exogenous chemical comprises a biologically active anion, a salt of formula VIII where Q is that anion is an option providing both the exogenous chemical and second excipient substance. An example is the tetrabutylammonium salt of glyphosate.
Other quaternary ammonium compounds that may be useful include compounds having a single C12-22 hydrocarbyl group and three C1-4 alkyl groups attached to the quaternary nitrogen atom. One or more of the C1-4 alkyl groups in such compounds can be replaced by a benzyl group. Specific examples include cetyltrimethylammonium bromide and benzalkonium chloride. Yet other quaternary ammonium compounds useful as the second excipient substance include compounds of formula I, where the first excipient substance is not of formula I.
Preferred quaternary ammonium compounds useful as the second excipient substance are compounds of formula V. where the first excipient substance is not of formula V. The same specific compounds of formula V are especially preferred whether a compound of formula V is the first or the second excipient substance. Particularly good results have been obtained where the first excipient substance is lecithin and the second excipient substance is Fluorad FC-135 or FC-754 or chemical equivalents thereof
Another class of compound useful as the second excipient substance is an amide or ester of formula VII above.
R14 in formula VII is preferably aliphatic and has about 7 to about 21 carbon atoms, more preferably about 13 to about 21 carbon atoms. It is especially preferred that R14 be a saturated straight-chain alkyl group. R15 is preferably an aliphatic group having 1-6 carbon atoms, more preferably alkyl or alkenyl having 2-4 carbon atoms. An especially preferred compound of formula VII for use as the second excipient substance is butyl stearate.
As compounds of formula VII, including butyl stearate, are generally oily liquids, aqueous compositions containing them are typically emulsions having at least one aqueous phase and at least one oil phase. with the compound of formula VII being present predominantly in the oil phase. Such emulsions may be water-in-oil, oil-in-water or water-in-oil-in-water (W/O/W) multiple emulsions.
Aqueous concentrate compositions where the first excipient substance is an alkylether of formula VI and the second excipient substance, if present, is a fatty acid ester of formula VII are limited in the degree to which an exogenous chemical such as glyphosate can be loaded. At some point, as the loading of exogenous chemical is increased, the composition will not remain suitably stable. Addition of a small amount of colloidal particulate to such compositions has surprisingly been found to greatly increase loading ability while retaining desired stability. Oxides of silicon, aluminum and titanium are preferred colloidal particulate materials. Particle size is preferably such that specific surface area is in the range from about 50 to about 400 m2/g. Where the exogenous chemical is glyphosate, the use of colloidal particulate enables loadings of at least 30% by weight for compositions containing sufficient alkylether and fatty acid ester to show enhanced herbicidal effectiveness, or at least 40% for compositions containing alkylether but no fatty acid ester and showing herbicidal effectiveness at least equal to current commercial products loaded at about 30%. We have found especially useful improvement in storage stability can be obtained using colloidal particulates having specific surface area between about 180 and about 400 m2/g.
Other means of improving stability of highly loaded compositions comprising an alkylether of formula VI, with or without a fatty acid ester, may also be possible and are within the scope of the present invention.
Compositions in accordance with the present invention are typically prepared by combining water. the exogenous chemical (unless it is a formulation which will not contain an exogenous chemical) and the aggregate-forming substance. Where the aggregate-forming substance is one that disperses readily in water, as is the case for example with Fluorad FC-135 or Fluorad FC-754, simple mixing with mild agitation may be sufficient. However, where the aggregate-forming substance requires high shear to disperse in water, as is the case for example with most forms of lecithin, it is presently preferred to sonicate or microfluidize the aggregate-forming substance in water. This can be done before or after a surfactant and/or the exogenous chemical is added. The sonication or microfluidization will generally produce liposomes or other aggregate structures other than simple micelles. The precise nature, including average size, of liposomes or other aggregates depends among other things on the energy input during sonication or microfluidization. Higher energy input generally results in smaller liposomes. Although it is possible to entrap or otherwise bind loosely or tightly the exogenous chemical in or on liposomes or with other supramolecular aggregates, the exogenous chemical does not need to be so entrapped or bound, and in fact the present invention is effective when the exogenous chemical is not entrapped or bound in the aggregates at all.
In a particular embodiment of the invention, the liposomes or other aggregates have an average diameter of at least 20 nm, more preferably at least 30 nm. We have determined by light scattering that certain liposomal compositions of the invention have average liposome diameters ranging from 54 to 468 nm as calculated using linear fit and from 38 to 390 nm as calculated using quadratic fit.
The concentrations of the various components will vary, in part depending on whether a concentrate is being prepared that will be further diluted before spraying onto a plant, or whether a solution or dispersion is being prepared that can be sprayed without further dilution.
In an aqueous glyphosate formulation that includes a dialkyl surfactant, for example a cationic dialkyl surfactant of formula I, suitable concentration ranges are: glyphosate 0.1-400 grams acid equivalent (a.e.)/liter, and dialkyl surfactant 0.001-10% by weight. In an aqueous glyphosate formulation using a cationic fluoro-organic surfactant and lecithin, suitable concentrations can be: glyphosate 0.1-400 g a.e./l, fluoro-organic surfactant 0.001-10% by weight, and soybean lecithin 0.001-10% by weight.
In an aqueous glyphosate formulation that includes a C16-18 alkylether surfactant and butyl stearate, suitable concentrations can be: glyphosate 0.1-400 g a.e./l, alkylether surfactant 0.001-10% by weight, and butyl stearate 0.001-10% by weight. To achieve the higher concentrations in these ranges, it is often beneficial to add other ingredients to provide acceptable storage stability, for example colloidal particulate silica or aluminum oxide at 0.5-2.5% by weight. In an aqueous glyphosate formulation that includes a C16-18 alkylether surfactant but no butyl stearate, glyphosate concentration can suitably be increased to 500 g a.e./l or more, in the presence of a colloidal particulate at 0.5-2.5% by weight.
In solid glyphosate formulations, higher concentrations of ingredients are possible because of the elimination of most of the water.
Weight/weight ratios of ingredients may be more important than absolute concentrations. For example, in a glyphosate formulation containing lecithin and a cationic fluoro-organic surfactant, the ratio of lecithin to glyphosate a.e. is in the range from about 1:3 to about 1:100. It is generally preferred to use a ratio of lecithin to glyphosate a.e. close to as high as can be incorporated in the formulation while maintaining stability, in the presence of an amount of the fluoro-organic surfactant sufficient to give the desired enhancement of herbicidal effectiveness. For example, a lecithin/glyphosate a.e. ratio in the range from about 1:3 to about 1:10 will generally be found useful, although lower ratios, from about 1:10 to about 1:100 can have benefits on particular weed species in particular situations. The ratio of fluoro-organic surfactant, when present, to glyphosate a.e. is likewise preferably in the range from about 1:3 to about 1:100. Because fluoro-organic surfactants tend to have relatively high cost, it will generally be desirable to keep this ratio as low as possible consistent with achieving the desired herbicidal effectiveness.
The ratio of fluoro-organic surfactant, where present, to lecithin is preferably in the range from about 1:10 to about 10:1, more preferably in the range from about 1:3 to about 3:1 and most preferably around 1:1. The ranges disclosed herein can be used by one of skill in the art to prepare compositions of the invention having suitable concentrations and ratios of ingredients. Preferred or optimum concentrations and ratios of ingredients for any particular use or situation can be determined by routine experimentation.
Although the combination of the components might be done in a tank mix, it is preferred in the present invention that the combination be made further in advance of the application to the plant, in order to simplify the tasks required of the person who applies the material to plants. We have found, however, that in some cases the biological effectiveness of a liposome-containing composition prepared from scratch as a dilute spray composition is superior to that of a composition having the same ingredients at the same concentrations but diluted from a previously prepared concentrate formulation.
Although various compositions of the present invention are described herein as comprising certain listed materials, in some preferred embodiments of the invention the compositions consist essentially of the indicated materials.
Optionally, other agriculturally acceptable materials can be included in the compositions. For example, more than one exogenous chemical can be included. Also, various agriculturally acceptable adjuvants can be included, whether or not their purpose is to directly contribute to the effect of the exogenous chemical on a plant. For example, when the exogenous chemical is a herbicide, liquid nitrogen fertilizer or ammonium sulfate might be included in the composition. As another example, stabilizers can be added to the composition. In some instances it might be desirable to include microencapsulated acid in the composition, to lower the pH of a spray solution on contact with a leaf. One or more surfactants can also be included. Surfactants mentioned here by trade name, and other surfactants that can be useful in the method of the invention, are indexed in standard reference works such as McCutcheon""s Emulsifiers and Detergents, 1997 edition, Handbook of Industrial Surfactants, 2nd Edition, 1997, published by Gower, and International Cosmetic Ingredient Dictionary, 6th Edition, 1995.
The compositions of the present invention can be applied to plants by spraying, using any conventional means for spraying liquids, such as spray nozzles, atomizers, or the like. Compositions of the present invention can be used in precision farming techniques, in which apparatus is employed to vary the amount of exogenous chemical applied to different parts of a field, depending on variables such as the particular plant species present, soil composition, and the like. In one embodiment of such techniques, a global positioning system operated with the spraying apparatus can be used to apply the desired amount of the composition to different parts of a field.
The composition at the time of application to plants is preferably dilute enough to be readily sprayed using standard agricultural spray equipment. Preferred application rates for the present invention vary depending upon a number of factors, including the type and concentration of active ingredient and the plant species involved. Useful rates for applying an aqueous composition to a field of foliage can range from about 25 to about 1,000 liters per hectare (l/ha) by spray application. The preferred application rates for aqueous solutions are in the range from about 50 to about 300 l/ha.
Many exogenous chemicals (including glyphosate herbicide) must be taken up by living tissues of the plant and translocated within the plant in order to produce the desired biological (e.g., herbicidal) effect. Thus, it is important that a herbicidal composition not be applied in such a manner as to excessively injure and interrupt the normal functioning of the local tissue of the plant so quickly that translocation is reduced. However, some limited degree of local injury can be insignificant, or even beneficial, in its impact on the biological effectiveness of certain exogenous chemicals.
A large number of compositions of the invention are illustrated in the Examples that follow. Many concentrate compositions of glyphosate have provided sufficient herbicidal effectiveness in greenhouse tests to warrant field testing on a wide variety of weed species under a variety of application conditions. Water-in-oil-in-water multiple emulsion compositions tested in the field have included:
The above compositions were prepared by process (vi) as described in the Examples.
Aqueous compositions tested in the field having an alkylether surfactant as the first excipient substance and/or containing a fatty acid ester have included:
The above compositions were prepared by process (vii) if they contain fatty acid ester and by process (viii) if they do not. Both processes are described in the Examples.
Aqueous compositions tested in the field containing colloidal particulates have included:
Aqueous compositions tested in the field having soybean lecithin (45% phospholipid, Avanti) as the first excipient substance and a cationic fluoro-organic surfactant as the second excipient substance have included:
The above compositions were prepared by process (v) as described in the Examples.
Aqueous compositions tested in the field having soybean lecithin (45% phospholipid, Avanti) as the first excipient substance and fatty acid ester as the second excipient substance have included:
The above compositions were prepared by process (x) as described in the Examples.
Dry compositions tested in the field have included:
The above compositions were prepared by the process described for dry granular compositions in the Examples.